# Characterization of the roles and regulation of Draxin in cranial neural crest

> **NIH NIH K99** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2021 · $85,622

## Abstract

PROJECT SUMMARY/ABSTRACT
 The neural crest (NC) is a stem cell population that originates within the forming central nervous
system. NC cells delaminate from the neuroepithelium by undergoing a spatiotemporally regulated epithelial—
mesenchymal transition (EMT) to exit from the neural tube. Cranial NC cells, which arise in the head region of
the embryo and are the only NC population in vivo with the ability to differentiate into craniofacial skeleton and
cartilage, are indispensable for the development of the face; mutations affecting NC development result in
numerous diseases and malformations affecting the craniofacial structures. The focus of my postdoctoral work
has been to study the mechanisms that control and facilitate cranial NC EMT. During the first phase of my
postdoctoral training, I have shown that this developmental EMT program is controlled by temporally restricted
expression of the Wnt antagonist, Draxin. A hallmark of Draxin's function during EMT is its transient expression
and rapid downregulation; perdurance of Draxin has deleterious effects on cranial NC EMT through
dysregulation of downstream targets of canonical Wnt signaling. Through the support of the K99, I discovered
that the transience of Draxin expression in cranial NC is mediated post-transcriptionally via its 3'-untranslated
region (UTR). Importantly, Draxin is stabilized by the RNA-binding protein Elavl1/HuR at the premigratory
stage, then targeted to cytoplasmic processing bodies (P-bodies) for decay to drive proper cranial NC EMT.
Collectively, these discoveries begin to unravel a new mechanism whereby cranial NC EMT is regulated
through post-transcriptional regulatory mechanisms balancing stability and decay of a molecular rheostat,
Draxin. COVID-19 research restrictions and university closures severely delayed my career plans and
development. Through the support of the K99, I completed many of the goals proposed in Aims 1 and 3 of my
original proposal, which sought to illuminate the interaction between Draxin and Wnt signaling, and the
regulation Draxin expression, respectively. However, COVID-19 research restrictions severely delayed the
completion of Aim 1 and progress of Aim 2, which sought to apply time-lapse and advanced microscopy
techniques (e.g. FRET) to more fully explore Draxin function. Further, completion of Aim 3 and publication of
these studies requires additional experiments in single-molecule imaging and RIP-seq. A funding extension
would allow me to develop critical new skills in advanced microscopy and RIP-seq to gain a mechanistic
understanding of Draxin activity during cranial NC EMT, and allow me to comple the revision experiments
necessary to publish the work performed under the parent K99 award to help me secure a tenure-track faculty
position, establish a vibrant independent research program in the developmental signaling field, and better
equip me with the knowledge necessary to transition into the study of cranial NC development and migr...

## Key facts

- **NIH application ID:** 10400365
- **Project number:** 3K99DE028592-02S1
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Erica Hutchins
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $85,622
- **Award type:** 3
- **Project period:** 2021-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400365

## Citation

> US National Institutes of Health, RePORTER application 10400365, Characterization of the roles and regulation of Draxin in cranial neural crest (3K99DE028592-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10400365. Licensed CC0.

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